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Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: Possible implication on migration and proliferation.

ABSTRACT: Background:Glioblastoma represents the most common primary brain tumor with a worst prognosis despite developments in neurosurgery and chemoradiotherapy. Detachment of the cells from the primary tumor tissue is a prerequisite for their dispersion and spreading. Initial and incessant dispersal of tumor cells from the primary tumor tissue renders GBM refractory to comprehensive surgical removal and increases the chance of recurrence and poorer prognosis. Purposes:The current study was designed to investigate the effect of inhibition of MEK-ERK1/2 signaling by PD98059 and U0126 on the growth and migration of glioma cells as well as their adhesion to extracellular matrix. Methods:MEK-ERK1/2 signaling in U87-MG cells was inhibited by PD98059 and U0126. Migration, proliferation and adhesion were analyzed by scratch-wound assay, MTT assay, cell adhesion assay respectively. Results:PD98059 and U0126 significantly not only reduced the proliferation of glioma cells and attenuated their migration but also increased their adhesion to gelatin of extracellular matrix. Conclusion:This study provides the evidence that inhibition of MEK-ERK1/2 signaling enhances the adhesion of glioma cells to gelatin/collagen component of ECM, and decreases the proliferation and migration of the glioma cells. We propose the possible rationale of association between ERK signaling and cell-cell adhesion molecules in glioma microenvironment which regulates the glioma initiation, growth and progression.

SUBMITTER: Ramaswamy P

PROVIDER: S-EPMC6894623 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: Possible implication on migration and proliferation.

Ramaswamy Palaniswamy P Nanjaiah Nandakumar Dalavaikodihalli ND Borkotokey Monjuri M

Annals of neurosciences 20190401 2

<h4>Background</h4>Glioblastoma represents the most common primary brain tumor with a worst prognosis despite developments in neurosurgery and chemoradiotherapy. Detachment of the cells from the primary tumor tissue is a prerequisite for their dispersion and spreading. Initial and incessant dispersal of tumor cells from the primary tumor tissue renders GBM refractory to comprehensive surgical removal and increases the chance of recurrence and poorer prognosis.<h4>Purposes</h4>The current study w ...[more]

PMID: 31975773

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Project description:Retinoblastoma (RB) is a common neoplasm that is exhibited in individuals globally. Increasing evidence demonstrated that cyclin‑dependent kinase regulatory subunit 1B (CKS1B) may be involved in the pathogenesis of various tumor types, including multiple myeloma and breast cancer. In the present study, the hypothesis that CKS1B downregulation would effectively inhibit the proliferation, invasion and angiogenesis of RB cells through the mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑regulated kinase (ERK) signaling pathway was examined. Initial investigation of the expression profile of CKS1B in RB and adjacent retina tissues was performed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. A total of three RB cell lines, SO‑RB50, Y79 and HXO‑RB44, were examined for selection of the cell line with the highest expression of CKS1B, and human normal retinal vascular endothelial cells (ACBRI‑181) were also evaluated. CKS1B short hairpin RNA (shRNA) sequences (shRNA CKS1B‑1, shRNA CKS1B‑2 and shRNA CKS1B‑3) and negative control shRNA sequences were constructed and transfected into cells at the third generation to evaluate the role of shCKS1B and the MEK/ERK signaling pathway in RB. Furthermore, the effect of shCKS1B on cell proliferation, migration, invasion, apoptosis and angiogenesis was investigated. CKS1B was determined to be highly expressed in RB tissue, compared with adjacent retina tissue. SO‑RB50 and HXO‑RB44 cells treated with shRNA CKS1B‑1 and shRNA CKS1B‑2 were selected for the present experiments. Activation of the MEK/ERK signaling pathway increases the expression of MEK, ERK, B‑cell lymphoma 2, proliferating cell nuclear antigen, cyclin D1, vascular endothelia growth factor and basic fibroblast growth factor, enhances cell proliferation, migration, invasion and lumen formation, and decreases apoptosis. Following silencing CKS1B, the aforementioned conditions were reversed. The key observations of the present study demonstrated that shCKS1B can inhibit the proliferation, invasion and angiogenesis of RB cells by suppressing the MEK/ERK signaling pathway. Thus, CKS1B represents a potential research target in the development of therapeutics for RB.

Project description:Purpose:B7 homologue 6 (B7-H6) has been found at an up-regulated level in multiple cancer cells and identified to be positively correlated with inferior clinical features. In non-Hodgkin lymphoma (NHL), however, the roles of B7-H6 and the underlying mechanism of action remain unclear. Through in vivo and in vitro experiments, the aim of this study was to explore the regulatory mechanism of B7-H6 in NHL in order to provide new therapeutic strategies that can potentially be applied in clinical practice. Methods:The expression of B7-H6 in T-lymphoblastic lymphoma (TLBL), diffuse large B cell lymphoma (DLBCL) and lymph node reactive hyperplasia (LRH) tissues were compared by immunohistochemistry. A total of 10 NHL cell lines were screened by Western blot to evaluate the expression of B7-H6. The effects of B7-H6 knockdown on cell proliferation, migration and invasion of NHL cells were studied in vivo using a transplanted tumor mice model, and in vitro by Cell Counting Kit-8 (CCK-8) and Transwell assays. Quantitative phosphoproteomics was performed to identify the changes of protein phosphorylation and related pathways affected by B7-H6. The effects of B7-H6 on NHL were validated via B7-H6 overexpression and pathway inhibitor assays. Results:The expression levels of B7-H6 in NHL cell lines, and TLBL and DLBCL tissues were significantly increased compared with those in the control groups. Inhibition of cell proliferation, migration and invasion was observed in Jurkat and Raji cells with B7-H6 knockdown. The ability of B7-H6 in promoting tumorigenesis was further validated by in vivo experiments. In addition, Ras and HIF-1 signaling pathways were shown to be significantly affected by B7-H6 through quantitative phosphorylation proteomics analysis. Ras/MEK/ERK pathway was verified to be significantly inhibited after B7-H6 knockdown by Western blot analysis. Strikingly, MEK inhibitor AZD8330 was found to have the ability to sufficiently inhibit Ras/MEK/ERK pathway, partially reverse cell proliferation and completely reverse cell migration and invasion induced by B7-H6. Conclusion:B7-H6 promotes cell proliferation, migration and invasion in NHL via Ras/MEK/ERK pathway. Hence, B7-H6 or Ras/MEK/ERK pathway targeting may be used as potential therapeutics for treating NHL.

Dataset Information

Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: Possible implication on migration and proliferation.

Publications

Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: Possible implication on migration and proliferation.

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